tbuckley/cabot-search huggingface dataset:
A Latter-Day Tolstoi
Authors: Alister Brass
Journal: JAMA (1970)

<i>The Cancer Ward</i>is not just another novel about a hospital, despite its standard cast of "character" patients, flirtatious nurses, and dedicated doctors. Rather it mirrors the whole of life in contemporary Russia, reflected from the mind of an intelligent, highly gifted writer. And it is, perhaps, ironic confirmation of Aleksandr Solzhenitsyn's success in accurately capturing that reflection that he has recently been expelled from the Soviet Writer's Union. In his earlier books,<i>One Day in the Life of Ivan Denisovitch and The First Circle</i>, Solzhenitsyn described life first in a Siberian prison camp and second in a special prison for technological experts during Stalin's reign of terror. Both novels were based on the author's own experience in such establishments after having been indiscreet enough to criticize Stalin in personal letters. For the framework of<i>Cancer Ward</i>, Solzhenitsyn similarly uses observations made while a patient in a hospital in Tashkent,
Evaluation of a Radioimmunoassay for α&lt;sub&gt;1&lt;/sub&gt;-Acid Glycoprotein To Monitor Therapy of Cancer Patients&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Patricia A. Ganz, M.D., William E. Shell, M.D., Zoltán A. Tökés, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1983)

A new radioimmunoassay for α1-acid glycoprotein (AGP) for monitoring the therapy of cancer patients was evaluated. Plasma levels of this glycoprotein were measured in 49 normal healthy volunteers, 71 patients with illnesses other than cancer, 190 patients with solid tumors, and 58 patients with hematologic neoplasms. Plasma levels of AGP were elevated in 89% of the solid tumor patients and 87% of the patients with hematologic neoplasms who had newly diagnosed, locally recurrent, or metastatic cancer. Only 18% of patients with illnesses other than cancer and normal renal function had elevations of plasma AGP. Serial measurements of AGP may be useful for monitoring therapy in several tumor types, including small-cell lung cancer, colon cancer, lymphoma, and non-small-cell lung cancer.
How effective is measles immunisation.
Authors: M D Coulter, B M Jones
Journal: BMJ (1977)

immigrant children' give a rate of 2 66 per 1000 to be compared with a rate of 0-33 per 1000 from 86 notifications in 263 000 indigenous children.2Far from being lower, the incidence of tuberculosis is eight times higher.As for tuberculin sensitivity, the annual acceptance rate for BCG protection of new- born infants in hospital, so far as our records go, has only once exceeded 70 %.3Either the 96 % BCG acceptance rate for Scottish children in table V is a misprint or the group was unusually highly selected.The authors report that 11 % of "Scottish" children live at a density of over six persons per room, 380% over four persons per room,
Steroid Therapy in Uremic Pericarditis
Authors: Gudmundur Eliasson
Journal: JAMA (1974)

PERICARDITIS and pericardial effusion complicating uremia are usually treated with frequent dialysis, rest, and supportive care. More aggressive therapy consists of pericardiocentesis, pericardial catheterization, pericardial window, or pericardiectomy. The use of steroids has been reported with varying results.<sup>1,2</sup>We report cases of three patients with uremic pericarditis who had effusion resistant to usual treatment, and who were treated with systemically given steroids. The response was dramatic. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 54-year-old white man was admitted to the hospital on June 6, 1972, with oliguric renal failure and uremia. A renal biopsy showed proliferative glomerulonephritis with crescents. There was no clinical or laboratory evidence of previous streptococcal infection or collagen vascular disease. He was initially treated with peritoneal dialysis. On June 18, he developed substernal chest pain, a temperature of 38 C (100.5 F), and a pericardial friction rub. An electrocardiogram showed nonspecific ST-T changes. A chest x-ray
Intravascular Factors in Diabetic Retinopathy
Authors: Samuel Vaisrub
Journal: JAMA (1975)

Not all vascular complications of diabetes are specific to this disease. Atherosclerosis of the coronary arteries in diabetic patients does not differ from that in the nondiabetic; it is merely more frequent. Specific, however, are the changes in the microvasculature. It is therefore not surprising that much attention has centered on these changes in diabetic retinopathy. Some of this attention is being currently diverted from vessel wall to vessel content, particularly to the fibrinolytic and clotting systems. It is becoming increasingly apparent that fibrinolytic activity and platelet aggregation may play an important pathogenetic role in the capillary closure,<sup>1</sup>which is one of the earliest manifestations of diabetic retinopathy. The fibrinolytic system is a defensive mechanism against vascular occlusion by platelet plugs and subsequent clots. Paul and Adlakha<sup>2</sup>found this activity to be decreased in two patients with diabetic retinopathy. Fukuda<sup>3</sup>reported similar observations in diabetic patients with
Job Specifications for the President of a County Medical Society
Authors: Ralph Crawshaw
Journal: JAMA (1976)

ANNUALLY evaluating the staff is one of the duties of the president of our local county medical society. While busily engaged in checking staff members' performance against responsibilities, it was discovered that there was no provision for judging the president. Of course, the society's bylaws specified he must be a member and must be elected, but beyond that—nothing. It is a curious fact of our culture that the higher the administrative responsibility, the less capacity is specified. Where there are no aptitude tests for president of the medical society, manufacturing company, or a government, yet there are hundreds for clerk-typists. The discrepancy can only be corrected by the presidential job-holders. Fortunately, after completing a year as president of a county medical society, the experience has revealed much about the position. Unfortunately, most of the learning has been sheer abrading experience; hopefully, to lessen this price for future county medical society
Focal Bone Marrow Activity
Authors: DAVID M. ROWE, DONALD S. SCHAUWECKER, HEE-MYUNG PARK
Journal: Clinical Nuclear Medicine (1985)

A 70-year-old man with known metastatic prostatic carcinoma presented with acute bleeding per rectum. A Tc-99m sulfur colloid gastrointestinal bleeding study appeared to show an initial focal area of activity in the right lower quadrant. When compared to the Tc-99m bone scan performed five days earlier, this activity is seen to represent a small focal area of remaining normal sulfur colloid bone marrow uptake simulating a bleeding site.
Distribution of Adenine Arabinoside and Interferon
Authors: Ann Arvin
Journal: JAMA (1979)

<h3>To the Editor.—</h3> In a recent issue ofThe Journal, Preblud et al (239:2551, 1978) commented on antiviral therapy for varicella in an immunocompromised host. In that letter to the editor, reference was made to the availability of adenine arabinoside and interferon for treatment of varicella and disseminated herpes zoster. The availability of these compounds warrants clarification. Adenine arabinoside and interferon are currently being investigated in double-blind, placebo-controlled trials to determine the potential usefulness of these compounds for treatment of chickenpox. Although both adenine arabinoside and interferon have been shown to alter the progression of natural events for herpes zoster,<sup>1-3</sup>there are no published efficacy data for either compound employed as treatment of chickenpox. Both compounds are being studied for treatment of varicella through controlled investigations at various institutions around the country. In addition, a double-blind prophylaxis study of interferon is being conducted for patients who are unable to
UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
Authors: Nicolas Duployez, Loïc Vasseur, Rathana Kim, Laëtitia Largeaud, Marie Passet, Anaïs L’Haridon, Pierre Lemaire, Laurène Fenwarth, Sandrine Geffroy, Nathalie Helevaut, Karine Celli‑Lebras, Lionel Adès, Delphine Lebon, Céline Berthon, Alice Marceau-Renaut, Meyling Cheok, Juliette Lambert, Christian Récher, Emmanuel Raffoux, Jean-Baptiste Micol, Arnaud Pigneux, Claude Gardin, Eric Delabesse, Jean Soulier, Mathilde Hunault, Hervé Dombret, Raphael Itzykson, Emmanuelle Clappier, Claude Preudhomme
Journal: Leukemia (2023)

Abstract Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF -TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF -TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3 -ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3 -ITD. UBTF -TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF -wild-type patients. In patients enrolled in the ALFA-0702 study ( n = 614 patients including 21 with UBTF -TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF -TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1 -mutated clones are frequently selected under ICT. This study supports the recognition of UBTF -TD AML as a new AML entity in adults.
An Automation Workflow for High‐Throughput Manufacturing and Analysis of Scaffold‐Supported 3D Tissue Arrays
Authors: Ruonan Cao, Nancy T. Li, Simon Latour, Jose L. Cadavid, Cassidy M. Tan, Ari Forman, Hartland W. Jackson, Alison P. McGuigan
Journal: Advanced Healthcare Materials (2023)

Abstract Patient‐derived organoids have emerged as a useful tool to model tumour heterogeneity. Scaling these complex culture models while enabling stratified analysis of different cellular sub‐populations, however, remains a challenge. One strategy to enable higher throughput organoid cultures is the scaffold‐supported platform for organoid‐based tissues (SPOT). SPOT allows the generation of flat, thin, and dimensionally‐defined microtissues in both 96‐ and 384‐well plate footprints that are compatible with longitudinal image‐based readouts. SPOT is currently manufactured manually, however, limiting scalability. In this study, an automation approach to engineer tumour‐mimetic 3D microtissues in SPOT using a liquid handler is optimized and comparable within‐ and between‐sample variation to standard manual manufacturing is shown. Further, a liquid handler‐supported cell extraction protocol to support single‐cell‐based end‐point analysis using high‐throughput flow cytometry and multiplexed cytometry by time of flight is developed. As a proof‐of‐value demonstration, 3D complex tissues containing different proportions of tumour and stromal cells are generated to probe the reciprocal impact of co‐culture. It is also demonstrated that primary patient‐derived organoids can be incorporated into the pipeline to capture patient‐level tumour heterogeneity. It is envisioned that this automated 96/384‐SPOT workflow will provide opportunities for future applications in high‐throughput screening for novel personalized therapeutic targets.
YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2
Authors: Xiaotang Wang, Wei Fan, Na Li, Yan Ma, Mudi Yao, Guoqing Wang, Siyuan He, Wanqian Li, Jun Tan, Qi Lu, Shengping Hou
Journal: Genome biology (2023)

Abstract Background Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying mechanisms are not entirely clear. Lactylation is a novel lactate-derived posttranslational modification that plays key roles in multiple cellular processes. Since hypoxia in ischemic retinopathy is a precipitating factor for retinal neovascularization, lactylation is very likely to be involved in this process. The present study aimed to explore the role of lactylation in retinal neovascularization and identify new therapeutic targets for retinal neovascular diseases. Results Microglial depletion by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 suppresses retinal neovascularization in oxygen-induced retinopathy. Hypoxia increased lactylation in microglia and accelerates FGF2 expression, promoting retinal neovascularization. We identify 77 sites of 67 proteins with increased lactylation in the context of increased lactate under hypoxia. Our results show that the nonhistone protein Yin Yang-1 (YY1), a transcription factor, is lactylated at lysine 183 (K183), which is regulated by p300. Hyperlactylated YY1 directly enhances FGF2 transcription and promotes angiogenesis. YY1 mutation at K183 eliminates these effects. Overexpression of p300 increases YY1 lactylation and enhances angiogenesis in vitro and administration of the p300 inhibitor A485 greatly suppresses vascularization in vivo and in vitro. Conclusions Our results suggest that YY1 lactylation in microglia plays an important role in retinal neovascularization by upregulating FGF2 expression. Targeting the lactate/p300/YY1 lactylation/FGF2 axis may provide new therapeutic targets for proliferative retinopathies.
Combination therapy for painful diabetic neuropathy is safe and effective
Authors: Helen Saul, Brendan Deeney, Candace Imison, Solomon Tesfaye
Journal: BMJ (2023)

The study Tesfaye S, Sloan G, Petrie J, et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet 2022;400:680-90. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/
Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation
Authors: Han Cong Seow, Jian-Piao Cai, Harry Weijie Pan, Cuiting Luo, Kun Wen, Jianwen Situ, Kun Wang, Hehe Cao, Susan W.S. Leung, Shuofeng Yuan, Jenny K.W. Lam
Journal: Journal of Controlled Release (2023)

Neutralising monoclonal antibody (mAb) is an important weapon in our arsenal for combating respiratory viral infections. However, the effectiveness of neutralising mAb has been impeded by the rapid emergence of mutant variants. Early administration of broad-spectrum mAb with improved delivery efficiency can potentially enhance efficacy and patient outcomes. WKS13 is a humanised mAb which was previously demonstrated to exhibit broad-spectrum activity against SARS-CoV-2 variants. In this study, a dual targeting formulation strategy was designed to deliver WKS13 to both the nasal cavity and lower airways, the two critical sites of infection caused by SARS-CoV-2. Dry powders of WKS13 were first prepared by spray drying, with cyclodextrin used as stabiliser excipient. Two-fluid nozzle (TFN) was used to produce particles below 5 μm for lung deposition (C-TFN formulation) and ultrasonic nozzle (USN) was used to produce particles above 10 μm for nasal deposition (C-USN formulation). Gel electrophoresis and size exclusion chromatography studies showed that the structural integrity of mAb was successfully preserved with no sign of aggregation after spray drying. To achieve dual targeting property, C-TFN and C-USN were mixed at various ratios. The aerosolisation property of the mixed formulations dispersed from a nasal powder device was examined using a Next Generation Impactor (NGI) coupled with a glass expansion chamber. When the ratio of C-TFN in the mixed formulation increased, the fraction of particles deposited in the lung increased proportionally while the fraction of particles deposited in the nasal cavity decreased correspondingly. A customisable aerosol deposition profile could therefore be achieved by manipulating the mixing ratio between C-TFN and C-USN. Dual administration of C-TFN and C-USN powders to the lung and nasal cavity of hamsters, respectively, was effective in offering prophylactic protection against SARS-CoV-2 Delta variant. Viral loads in both the lung tissues and nasal wash were significantly reduced, and the efficacy was comparable to systemic administration of unformulated WKS13. Overall, dual targeting powder formulation of neutralising mAb is a promising approach for prophylaxis of respiratory viral infections. The ease and non-invasive administration of dual targeting nasal powder may facilitate the widespread distribution of neutralising mAb during the early stage of unpredictable outbreaks.
A Photo‐Activated Thermoelectric Catalyst for Ferroptosis‐/Pyroptosis‐Boosted Tumor Nanotherapy
Authors: Xiaoyan Jiang, Muyue Yang, Ying Fang, Zhenyu Yang, Xinyue Dai, Ping Gu, Wei Feng, Yu Chen
Journal: Advanced Healthcare Materials (2023)

Abstract Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) has gradually come into the limelight for oncological treatment due to its noninvasiveness, high specificity, and low side effects. However, upregulated heat‐shock proteins (HSPs) and reactive oxygen species (ROS)‐defensing system such as glutathione (GSH) or MutT homolog 1 (MTH1) protein in tumor microenvironment counteract the efficiency of single‐modality therapy either PTT or PDT. Herein, the well‐defined bismuth telluride nanoplates (Bi 2 Te 3 NPs) are engineered with a high‐performance photo‐thermo‐electro‐catalytic effect for tumor‐synergistic treatment. Upon near‐infrared light illumination, Bi 2 Te 3 NPs induce a significant temperature elevation for PTT, which effectively inhibits MTH1 expression. Especially, heating and cooling alteration caused temperature variations result in electron–hole separation for ROS generation, which not only damages HSPs to reduce the thermotolerance for enhance PTT, but also arouses tumor cell pyroptosis. Additionally, Bi 2 Te 3 NPs conspicuously reduce GSH, further improving ROS level and leading to decrease glutathione peroxidase 4 (GPX4) activity, which triggers tumor cell ferroptosis. Due to the photo‐thermo‐electro‐catalytic synergistic therapy, Bi 2 Te 3 NPs are gifted with impressive tumor suppression on both ectopic and orthotopic ocular tumor models. This work highlights a high‐performance multifunctional energy‐conversion nanoplatform for reshaping tumor microenvironment to boost the tumor‐therapeutic efficacy of phototherapy.
FLT3 inhibitors upregulate CXCR4 and E-selectin ligands via ERK suppression in AML cells and CXCR4/E-selectin inhibition enhances anti-leukemia efficacy of FLT3-targeted therapy in AML
Authors: Yannan Jia, Weiguo Zhang, Mahesh Basyal, Kyung Hee Chang, Lauren Ostermann, Jared K Burks, Charlie Ly, Hong Mu-Mosley, Qi Zhang, Xin Han, William E Fogler, John L Magnani, Arnaud Lesegretain, Anna A Zal, Tomasz Zal, Michael Andreeff
Journal: Leukemia (2023)

Fms-like tyrosine kinase 3 inhibitor(s) (FLT3i), including sorafenib, quizartinib, and FDA-approved midostaurin and gilteritinib, are commonly used to treat adult acute myelogenous leukemia (AML) with FLT3 internal tandem duplication (ITD) mutations.These mutations are present in about 30% of adult AML cases and are associated with a poor prognosis [1].However, FLT3i are not very effective in eliminating leukemia blasts in bone marrow (BM) [2, 3], which suggests that interactions between AML blasts and the BM microenvironment (BMM) provide a sanctuary for AML cells and protect them from targeted therapies [4].BMM or "niche"-mediated resistance may result from the influence of extrinsic cytokines or chemokines, such as CXC chemokine receptor 4 (CXCR4)/CXC motif ligand 12 (CXCL12) and endothelial (E)-selectin (CD62E)/E-selectin ligands (E-selectin-L).Both CXCR4 and E-selectin ligands play crucial roles in directing leukocyte or hematopoietic stem cell (HSC) homing to BMM [5,6].In addition, the hypoxic condition (with oxygen levels of 1-3%) in BMM can also trigger the upregulation of genes glycosylating Eselectin-L through the hypoxia-inducible factor 1-α-a key transcriptional factor induced by hypoxia, known to be involved in the synthesis of the carbohydrate ligands for E-selectin and is associated with AML therapy resistance [7,8].We hypothesized that concomitantly targeting CXCR4 and E-selectin could enhance the anti-leukemia efficacy and alleviate the BM niche-mediated resistance to FLT3-targeted therapy.If this hypothesis is validated, this concept could serve as a backbone for developing combinatorial strategies with FLT3i as a frontline therapy for FLT3-mutant AML.To this end, we first investigated whether the baseline levels of CXCR4/E-selectin-L were associated with FLT3i resistance.Results showed that leukemia blasts from relapsed/refractory FLT3-
Microneedle-assisted vaccination combined with autophagy regulation for antitumor immunotherapy
Authors: Dan Yang, Minglong Chen, Ying Sun, Chaonan Shi, Wenhao Wang, Wanchen Zhao, Ting Wen, Ting Liu, Jintao Fu, Chao Lu, Chuanbin Wu, Guilan Quan, Xin Pan
Journal: Journal of Controlled Release (2023)
Multifunctional Hyaluronic Acid Microneedle Patch Embedded by Cerium/Zinc‐Based Composites for Accelerating Diabetes Wound Healing
Authors: Juan Yang, Zhaoyou Chu, Yechun Jiang, Wang Zheng, Jiangwei Sun, Lingling Xu, Yan Ma, Wanni Wang, Min Shao, Haisheng Qian
Journal: Advanced Healthcare Materials (2023)

Chronic nonhealing diabetic wounds are becoming increasingly severe, with high rates of mortality and disability, owing to the difficulty in wound healing caused by hyperglycemia, blocked angiogenesis, biofilm infection, and excessive oxidative stress. A multicomponent enzyme-responsive natural polymer, a hyaluronic acid (HA) microneedle, embedded in a cerium/zinc-based nanomaterial (ZCO) for the treatment of diabetic wounds is reported. ZCO-HA can destroy the oxidation balance of bacteria, kill bacteria, and scavenge reactive oxygen species (ROS) to alleviate oxidative stress via the adjustable release of Zn2+ and Ce3+ /4+ . Additionally, ZCO-HA exhibits good anti-inflammatory activity through the nuclear factor kappa-B (NF-κB) pathway, which reduces the inflammatory state of macrophages and promotes cell proliferation, migration, and angiogenesis. In vitro experiments shows that ZCO-HA accompanies mouse fibroblast migration, promoting human umbilical vein endothelial cell tube formation. In vivo studies in mice with streptozotocin-induced (STZ)-induced diabetes reveal that this microneedle accelerates wound healing without systemic toxicity. RNA transcriptome sequencing illustrates that the multicomponent HA microneedle accelerates wound healing in diabetes through cell migration and inhibits inflammatory reactions and oxidative damage in mice via the NF-κB signaling pathway.